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Derived from the integration of ethanol and non-ionic surfactants within their vesicular structures, ethoniosomes exhibit superior physicochemical stability, enhanced skin permeability, and the capacity to encapsulate both hydrophilic and lipophilic drugs. In this study, three quick, easy, affordable, and environmentally friendly spectrophotometric methodologies have been developed to simultaneously assess Donepezil HCl (DPZ) and pentoxifylline (PTX) in their pure form, synthetic mixtures and laboratory-prepared ethoniosome formulation with a remarkable degree of precision and accuracy. The iso-absorptive point, dual wavelength, and ratio subtraction methods are the three approaches that have been successfully developed and validated. For both DPZ and PTX, the concentrations were rectilinear over the range 1\u2013100\u00a0\u00b5g\/mL. Validation of the suggested methods has been carried out in accordance with ICH standards with regard to linearity, detection limit, quantification limit, precision, and accuracy. The evaluation of whiteness, blueness, and greenness measures confirmed that the recommended strategies show a significant advantage over previously published ones.<\/jats:p>","DOI":"10.1186\/s13065-026-01759-4","type":"journal-article","created":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T11:53:13Z","timestamp":1773489193000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Whiteness and greenness metric tools for assessment of the spectrophotometric methods sustainability: mathematical manipulation of absorption spectra to resolve the interfering donepezil HCl and pentoxifylline in ethoniosomes"],"prefix":"10.1186","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-6577-3499","authenticated-orcid":false,"given":"Mennah M. 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